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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 11th February 1992 to 3rd March 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study performed according to OECD test guideline No. 404 and in compliance with GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report Date:
1992

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
age and weight of animals not reported
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
age and weight of animals not reported
Principles of method if other than guideline:
not applicable
GLP compliance:
yes (incl. certificate)
Remarks:
UK GLP Compliance Programme (inspected on 1990-06-19/signed on 1990-10-05

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
liquid
Details on test material:
- Name of test material (as cited in study report): ST 02 C 88
- Substance type: pure active substance
- Physical state: colourless liquid
- Lot/batch No.: A/D/33906 (Toxicol reference N°)
- Storage condition of test material: ca. 4°C under nitrogen in the dark

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ranch Rabbits, Crawley Down, Sussex, England
- Age at study initiation: not reported
- Weight at study initiation: 2.9-4..0 kg bw
- Housing: rabbits were individually housed in grid bottomed metal cages.
- Diet (e.g. ad libitum): ad libitum (antibiotic-free rabbit diet (SQC Standard rabbit pellets produced by Special Diets Services, Witham, Essex) and certificate of analysis))
- Water (e.g. ad libitum): ad libitum (certificate of analysis)
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-21
- Humidity (%): 39-59
- Air changes (per hr): no data (air conditionned)
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: not reported

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL of pure test material
Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48, and 72 hours after patch removal. Additional examination on day 7 and 14.
Number of animals:
4 females (preliminary screen: 1 , main study: 3)
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- Type of wrap if used: The test patch (surgical lint) was held in position by encircling the trunk of the animal with a length of "Elastoplast" elastic adhesive bandage 7.5cm wide.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, gently cleaned using cotton wool soaked in warm water
- Time after start of exposure: 4 hours


OBSERVATION TIME POINTS
1, 24, 48, and 72 hours after patch removal. Additional examination on day 7 and 14.


SCORING SYSTEM:

Erythema and Eschar Formation:
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beef redness) to slight eschar formation (injuries in depth) 4

Oedema formation:
No oedema 0
Very slight oedema (barely perceptible) 1
Slight oedema (edges of area well defined by definite raising) 2
Moderate oedema (raised approximately 1mm) 3
Severe oedema (raised more than 1mm and extending beyond area of exposure) 4

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: desquamation observed after 7 days
Irritation parameter:
erythema score
Basis:
animal: #2 & #4
Time point:
24/48/72 h
Score:
2.67
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: desquamation and skin thickening observed after 7 and 14 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: desquamation observed after 7 and 14 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.33
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritant / corrosive response data:
One hour after the end of the dosing period, oedema was noted at the application site in 2 animals and, in one rabbit, this was accompanied by slight erythema.
Twenty-four hours after patch removal, erythema ranging in intensity from slight to moderate, accompanied by slight to moderate oedema, was apparent at the application site in all 4 animals. Over the next 24 hours these skin responses generally increased and, by the 72 hour observation, erythema was evident in 3 animals and well defined in the fourth. The the oedematous reaction varied from slight to Seven days after dosing, there was no sign of either erythema or oedema at the application site of the rabbit used in the preliminary screen and observations on this rabbit were discontinued at this stage. In the remaining 3 animals, well defined erythema and slight to moderate oedema were still apparent. Desquamation was noted at the application site in all 4 rabbits. Fourteen days after dosing, oedema was no longer apparent in any animal. Well defined or moderate erythema was noted in the 3 remaining animals and skin thickening and/or desquamation was observed at the application site in all these animals.
Other effects:
None

Any other information on results incl. tables

Table 7.3.1/1: Mean irritant/corrosive response data for each animals at each observation time up to removal of animals from the test

 

Score at time point / Reversibility

Erythema

Max. score 4

Edema

Max. score 4

1 h

0/0/1/0

0/0/2/1

24 h

1/2/3/2

2/2/3/1

48 h

1/3/3/3

2/2/3/2

72 h

2/3/3/3

1/3/3/2

Average 24h, 48h, 72h

1.33/2.67/3/2.67

1.67/2.33/3/1.67

7 d

0/2/2/2 a

0/1/3/2 a

14 d ($)

2b/2a/1b

0b/0a/0b

Reversibility*)

n.c.

c.

Average time (day) for reversion**

-

14 d

 *) Reversibility: c. = completely reversible; n.c. = not completely reversible; n. = not reversible

**): correspond to the last day for which skin irritation signs in the last animal were observed

a = desquamation was observed

b = desquamation and skin thickening

($) = seven day after dosing there were no sign of either erythema or edema at the appllication site of the rabbit used in the preliminary screen and observations of this rabbit were discontinued at this stage.

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
Under the test conditions, the test material is classified as Skin irr. Category 2 (H315: Causes skin irritation) according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP).
Executive summary:

In a dermal irritation study performed according to the EU B.4 test method and in compliance with GLP, 0.5 mL of undiluted test material was dermally applied on the clipped skin of the dorsal surface of the trunk of 4 New Zealand White rabbits.Test sites were covered with a semi-occlusive dressing for 4 hours. Animals were then observed for 14 days for oedema and erythema. 

Skin irritation was assessed and scored according to the Draize scale at 1, 24, 48 and 72 h after the removal of the patch. Additional assessments were carried out 7 and, in the last 3 animals dosed, 14 days after dosing to determine the degree of reversibility of the skin reaction.

The mean scores calculated for each animal tested within 3 scoring times (24, 48 and 72 h) were 1.33/2.67/3.00/2.67 for erythema and 1.67/2.33/3.00/1.67 for oedema.

 

One hour after the end of the dosing period, oedema was noted at the application site in 2 animals and, in one rabbit, this was accompanied by slight erythema. Twenty-four hours after patch removal, erythema ranging in intensity from slight to moderate, accompanied by slight to moderate oedema, was apparent at the application site in all 4 animals. Over the next 24 hours these skin responses generally increased and, by the 72 hour observation, erythema was evident in 3 animals and well defined in the fourth. The intensity of the oedematous reaction varied from slight to moderate. Seven days after dosing, there was no sign of either erythema or oedema at the application site of the rabbit used in the preliminary screen and observations on this rabbit were discontinued at this stage. In the remaining 3 animals, well defined erythema and slight to moderate oedema were still apparent. Desquamation was noted at the application site in all 4 rabbits. Fourteen days after dosing, oedema was no longer apparent in any animal. Well defined or moderate erythema was noted in the 3 remaining animals and skin thickening and/or desquamation was observed at the application site in all these animals.

 

Therefore, under the test conditions, the test material is classified as:

- Skin irr. Category 2 (H315: Causes skin irritation) according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP).

This study is considered as acceptable and satisfies the requirement for skin irritation endpoint.